An immunomodulating substance, a biological response modifier (BRM) or biotherapy is important for the treatment of cancer and infectious diseases. b-Glucan is a well-known BRM which is widely distributed in nature and used as a medicine and food. [1][2][3][4][5] The effects of "Lentinan" from Lentinus edodes and "Sonifilan" (SPG) from Schizophyllum commune in cancer therapy have been clinically proven.6,7) We have already developed b-glucans, GRN from Grifola frondosa, [8][9][10] SSG and TSG from Sclerotinia sclerotiorum, [11][12][13] OL-2 from Omphalia lapidescens, 14) PVS and PVG from Peziza vesiculosa, 15) CSBG from Candida spp., 16) OX-ZYM from a yeast cell preparation, zymosan, 17,18) and SCG from Sparaccis crispa. 19) We have also prepared several carboxymethyl, hydroxyethyl, sulfate, and polyol derivatives of the above b-glucans.20) In addition, we have analyzed the mechanism of b-glucan mediated immunopharmacological activity and identified the conformation dependent and independent activity. [21][22][23][24][25] These rather complicated relationships between structure and activity suggest the contribution of multiple receptor-ligand interactions in b-glucan mediated immunopotentiation.The incidence of cancer is gradually increasing and the spectrum of cancer-prone organs is changing each year. In addition to surgery, irradiation, and chemotherapy, immunotherapy is believed to be an important cancer therapy. 26)Immunotherapy and biotherapy include various approaches, such as BRMs, cytokines, lymphocyte transplantation, gene therapy, and herbal and alternative medicines. Clinical trials of these therapies are being widely carried out, and clinical evidence suggests their efficacy, although the precise mechanisms are still difficult to understand. The development of additional b-glucans is still needed for better biotherapy and to understand the molecular mechanisms.Agaricus blazei is a medical mushroom widely eaten and prescribed in Japan. There are various kind of health foods containing A. blazei and/or its extracts, but the molecular mechanisms of its action is far beyond complete understanding. The most anticipated pharmacological effect of A. blazei is modulation of the immune system against cancer. In the last decade, there have been several studies which focused on an antitumor polysaccharide from A. blazei, i.e., 1,6-b-glucan, glucan-protein complex, a-glucan, and heteroglycan. 27-34) Antitumor polysaccharides were screened not only in the fruitbody but also the liquid cultured medium and mycelium. One of the best characterized components, FIII-2-b, was prepared from the sodium hydroxide extract of the fruit body, and the structure was analyzed by methylation and NMR analyses. Contribution of a protein moiety to the activity of FIII-2-b was speculated by loss of the activity by partial formolysis. In the preliminary investigation, we have also determined that the major carbohydrate component of the fruit body of A. blazei is 1,6-b-glucan; however, we have already shown that a linear 1,6-b-glucan,...

The ability of grifolan (GRN), a purified fungal (1-->3)-beta-D-glucan, to induce various cytokines from macrophages was examined in vitro. Interleukin-6 (IL-6) activity in supernatants from the culture of macrophage cell line, RAW264.7 was dependent on increasing doses of GRN. The level of IL-6 induced with 500 micrograms/ml of GRN was comparable to that induced with lipopolysaccharide (LPS) 10 micrograms/ml. Enhancement of the mRNA level of IL-6 by treatment with GRN was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The effect of GRN on production of IL-6 was also observed using peritoneal macrophages from C3H/HeJ mice which did not respond to endotoxins. This data suggested that the ability of GRN to activate IL-6 production of macrophages is not due to contamination of endotoxins in the preparation. Enhanced production of cytokine by GRN was observed not only with IL-6, but also with interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). In the production of TNF alpha, GRN was more effective than LPS used in this study. Other soluble or gel-forming(1-->3)-beta-D-glucans from various sources did not enhance the production of such cytokines although they are structurally similar to GRN. The above results indicate that GRN is a novel macrophage activator which augments cytokine production without dependence on endotoxins.

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